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产品描述

来源:
Mouse
应用:
ELISA 1:10000, WB 1:500-1:2000, IHC 1:200-1:1000, IF/ICC 1:200-1:1000, FCM 1:200-1:400
*The optimal dilutions should be determined by the end user.
*Tips:

WB: 适用于变性蛋白样本的免疫印迹检测. IHC: 适用于组织样本的石蜡(IHC-p)或冰冻(IHC-f)切片样本的免疫组化/荧光检测. IF/ICC: 适用于细胞样本的荧光检测. ELISA(peptide): 适用于抗原肽的ELISA检测.

反应:
Human,Rat,Monkey
克隆:
Monoclonal [AFB1889]
特异性:
CDK5 antibody detects endogenous levels of total CDK5.
RRID:
AB_2833913
引用格式: Affinity Biosciences Cat# BF0121, RRID:AB_2833913.
偶联:
Unconjugated.
纯化:
Affinity-chromatography.
保存:
Mouse IgG1 in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
别名:

展开/折叠

Cdk 5; Cdk5; CDK5_HUMAN; Cell division protein kinase 5; Crk6; Cyclin dependent kinase 5; Cyclin-dependent kinase 5; Protein kinase CDK5 splicing; PSSALRE; Serine threonine protein kinase PSSALRE; Serine/threonine-protein kinase PSSALRE; Tau protein kinase II catalytic subunit; TPKII catalytic subunit;

抗原和靶标

免疫原:

Purified recombinant fragment of human CDK5 expressed in E. Coli.

Uniprot:
基因/基因ID:
表达:
Q00535 CDK5_HUMAN:

Isoform 1 is ubiquitously expressed. Accumulates in cortical neurons (at protein level). Isoform 2 has only been detected in testis, skeletal muscle, colon, bone marrow and ovary.

描述:
CDK5 is a protein kinase of the CDK family. Unlike other members of this family, it is not activated by cyclins but by p35 (CDK5R1) and p39. An important regulator of neuronal positioning during brain development. May also play a role in synaptogenesis and neurotransmission. Substrates include TAU, MAP2, NF-H and -M, Nudel, PDE6, beta-catenin, amphyphysin, dynamin I, synapsin 1, Munc-18, and NMDA receptor 2A. Plays a role in myogenesis, haematopoietic cell differentiation, spermatogenesis, insulin secretion, and lens differentiation. Implicated in the pathology of neurofibrillary tangles and formation of senile plaques, hallmarks of Alzheimer s disease. Induces tau phosphorylation and aggregation and neurofibrillary tangle deposition and neurodegeneration in in vitro and in vivo animal models. Brain samples from Alzeimer s pateints show elevated CDK5 activity.
序列:
MQKYEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEGVPSSALREICLLKELKHKNIVRLHDVLHSDKKLTLVFEFCDQDLKKYFDSCNGDLDPEIVKSFLFQLLKGLGFCHSRNVLHRDLKPQNLLINRNGELKLADFGLARAFGIPVRCYSAEVVTLWYRPPDVLFGAKLYSTSIDMWSAGCIFAELANAGRPLFPGNDVDDQLKRIFRLLGTPTEEQWPSMTKLPDYKPYPMYPATTSLVNVVPKLNATGRDLLQNLLKCNPVQRISAEEALQHPYFSDFCPP

翻译修饰 - Q00535 作为底物

Site PTM Type Enzyme
K3 Ubiquitination
K9 Acetylation
K9 Ubiquitination
T14 Phosphorylation
Y15 Phosphorylation P54764 (EPHA4) , P06241 (FYN) , Q16620 (NTRK2) , A0A173G4P4 (Abl fusion) , P00519 (ABL1)
T17 Phosphorylation
K20 Methylation
K20 Ubiquitination
K22 Methylation
K22 Ubiquitination
K33 Acetylation
K33 Ubiquitination
S46 Phosphorylation
S47 Phosphorylation
K56 Acetylation
K56 Ubiquitination
S72 Phosphorylation
K74 Ubiquitination
T77 Phosphorylation
K89 Ubiquitination
S105 Phosphorylation
K128 Ubiquitination
K141 Ubiquitination
S159 Phosphorylation P48729 (CSNK1A1)
K213 Ubiquitination
S229 Phosphorylation
T231 Phosphorylation
K232 Ubiquitination
K237 Ubiquitination
Y239 Phosphorylation
Y242 Phosphorylation
K254 Ubiquitination
K268 Ubiquitination
C290 S-Nitrosylation

翻译修饰 - Q00535 作为激酶

Substrate Site Source
O00429 (DNM1L) S616 Uniprot
O14939 (PLD2) S134 Uniprot
O15169 (AXIN1) T481 Uniprot
O15516 (CLOCK) T451 Uniprot
O15516 (CLOCK) T461 Uniprot
O43464 (HTRA2) S400 Uniprot
O43602-2 (DCX) S28 Uniprot
O43602-1 (DCX) S287 Uniprot
O43602-2 (DCX) T289 Uniprot
O43602-1 (DCX) S297 Uniprot
O43602-1 (DCX) S306 Uniprot
O43602-2 (DCX) T321 Uniprot
O43602-1 (DCX) T326 Uniprot
O43602-2 (DCX) S327 Uniprot
O43602-2 (DCX) T331 Uniprot
O43602-1 (DCX) S332 Uniprot
O43602-2 (DCX) S334 Uniprot
O43602-1 (DCX) T336 Uniprot
O43602-1 (DCX) S339 Uniprot
O60260 (PRKN) S131 Uniprot
O60331 (PIP5K1C) S650 Uniprot
O75553-6 (DAB1) S491 Uniprot
O75553-6 (DAB1) S515 Uniprot
O94811 (TPPP) T14 Uniprot
O94811 (TPPP) S18 Uniprot
O94811 (TPPP) S160 Uniprot
O94916 (NFAT5) T135 Uniprot
P01106 (MYC) S62 Uniprot
P04150 (NR3C1) S203 Uniprot
P04150 (NR3C1) S211 Uniprot
P04150 (NR3C1) S226 Uniprot
P04156 (PRNP) S43 Uniprot
P04626 (ERBB2) S1174 Uniprot
P04637 (TP53) S15 Uniprot
P04637 (TP53) S20 Uniprot
P04637 (TP53) S33 Uniprot
P04637 (TP53) S46 Uniprot
P04637-1 (TP53) S315 Uniprot
P05067-4 (APP) T668 Uniprot
P05067-8 (APP) T724 Uniprot
P05067-1 (APP) T743 Uniprot
P06400 (RB1) S795 Uniprot
P06400 (RB1) S807 Uniprot
P06400 (RB1) S811 Uniprot
P07196 (NEFL) T21 Uniprot
P07814 (EPRS) S886 Uniprot
P08670 (VIM) S56 Uniprot
P10275 (AR) S83 Uniprot
P10275 (AR) S310 Uniprot
P10636-2 (MAPT) S144 Uniprot
P10636-2 (MAPT) T147 Uniprot
P10636-8 (MAPT) T153 Uniprot
P10636-6 (MAPT) T154 Uniprot
P10636-6 (MAPT) S156 Uniprot
P10636-6 (MAPT) T159 Uniprot
P10636-6 (MAPT) T173 Uniprot
P10636-2 (MAPT) S177 Uniprot
P10636-8 (MAPT) T181 Uniprot
P10636-8 (MAPT) S199 Uniprot
P10636-8 (MAPT) S202 Uniprot
P10636-8 (MAPT) T205 Uniprot
P10636-8 (MAPT) T212 Uniprot
P10636-8 (MAPT) S214 Uniprot
P10636-8 (MAPT) T217 Uniprot
P10636-8 (MAPT) T231 Uniprot
P10636 (MAPT) S235 Uniprot
P10636-8 (MAPT) S262 Uniprot
P10636-2 (MAPT) T284 Uniprot
P10636-2 (MAPT) S307 Uniprot
P10636-2 (MAPT) S315 Uniprot
P10636-6 (MAPT) T315 Uniprot
P10636-6 (MAPT) S338 Uniprot
P10636-6 (MAPT) S346 Uniprot
P10636-8 (MAPT) T373 Uniprot
P10636-8 (MAPT) S396 Uniprot
P10636-8 (MAPT) S404 Uniprot
P10636-8 (MAPT) S409 Uniprot
P10636-8 (MAPT) S422 Uniprot
P10636 (MAPT) T498 Uniprot
P10636 (MAPT) S516 Uniprot
P10636 (MAPT) S519 Uniprot
P10636 (MAPT) T522 Uniprot
P10636 (MAPT) T529 Uniprot
P10636 (MAPT) S531 Uniprot
P10636 (MAPT) T534 Uniprot
P10636 (MAPT) T548 Uniprot
P10636 (MAPT) S552 Uniprot
P10636 (MAPT) S713 Uniprot
P10636 (MAPT) S721 Uniprot
P12931 (SRC) S75 Uniprot
P14416 (DRD2) S321 Uniprot
P15311 (EZR) T235 Uniprot
P15927 (RPA2) S23 Uniprot
P15927 (RPA2) S29 Uniprot
P15927 (RPA2) S33 Uniprot
P16949 (STMN1) S38 Uniprot
P17600-2 (SYN1) S62 Uniprot
P17600-1 (SYN1) S67 Uniprot
P17600-2 (SYN1) S551 Uniprot
P17600 (SYN1) S553 Uniprot
P17706-3 (PTPN2) S304 Uniprot
P21860-1 (ERBB3) T873 Uniprot
P21860-1 (ERBB3) S1123 Uniprot
P26358 (DNMT1) S154 Uniprot
P27695 (APEX1) T233 Uniprot
P29474 (NOS3) S114 Uniprot
P31146 (CORO1A) T424 Uniprot
P35222 (CTNNB1) S191 Uniprot
P35222 (CTNNB1) S246 Uniprot
P35612 (ADD2) S604 Uniprot
P35612 (ADD2) S617 Uniprot
P35612 (ADD2) S701 Uniprot
P35968 (KDR) S229 Uniprot
P37231 (PPARG) S273 Uniprot
P40763 (STAT3) S727 Uniprot
P41143 (OPRD1) T161 Uniprot
P41236 (PPP1R2) T73 Uniprot
P42858 (HTT) S432 Uniprot
P42858 (HTT) S1179 Uniprot
P42858 (HTT) S1199 Uniprot
P46527 (CDKN1B) T187 Uniprot
P47989 (XDH) T222 Uniprot
P48681 (NES) T315 Uniprot
P48681 (NES) T1299 Uniprot
P49023 (PXN) S85 Uniprot
P49023-2 (PXN) S244 Uniprot
P49418-1 (AMPH) S272 Uniprot
P49418-1 (AMPH) S276 Uniprot
P49418-2 (AMPH) S285 Uniprot
P49757 (NUMB) S288 Uniprot
P49768 (PSEN1) T354 Uniprot
P53779-3 (MAPK10) T93 Uniprot
P53779-2 (MAPK10) T131 Uniprot
P56817 (BACE1) T252 Uniprot
P62136 (PPP1CA) T320 Uniprot
Q00536-1 (CDK16) S95 Uniprot
Q00536-3 (CDK16) S101 Uniprot
Q02078-5 (MEF2A) S400 Uniprot
Q02078 (MEF2A) S408 Uniprot
Q02750-1 (MAP2K1) T286 Uniprot
Q02750 (MAP2K1) T292 Uniprot
Q05193-1 (DNM1) S774 Uniprot
Q05193-1 (DNM1) S778 Uniprot
Q05193 (DNM1) T780 Uniprot
Q05397 (PTK2) S732 Uniprot
Q05397 (PTK2) S910 Uniprot
Q12778 (FOXO1) S249 Uniprot
Q12879-1 (GRIN2A) S1232 Uniprot
Q13153-1 (PAK1) T212 Uniprot
Q13315 (ATM) S794 Uniprot
Q13522 (PPP1R1A) S67 Uniprot
Q13794 (PMAIP1) S13 Uniprot
Q14194 (CRMP1) T509 Uniprot
Q14194 (CRMP1) S522 Uniprot
Q14195 (DPYSL3) T509 Uniprot
Q14195 (DPYSL3) T514 Uniprot
Q14195 (DPYSL3) S518 Uniprot
Q14195 (DPYSL3) S522 Uniprot
Q14814 (MEF2D) S444 Uniprot
Q15078 (CDK5R1) S8 Uniprot
Q15078 (CDK5R1) T138 Uniprot
Q15717 (ELAVL1) S202 Uniprot
Q15833 (STXBP2) T572 Uniprot
Q16236 (NFE2L2) T395 Uniprot
Q16236 (NFE2L2) S433 Uniprot
Q16236 (NFE2L2) T439 Uniprot
Q16555 (DPYSL2) S522 Uniprot
Q16643 (DBN1) S142 Uniprot
Q3V6T2 (CCDC88A) S1675 Uniprot
Q5S007 (LRRK2) S1627 Uniprot
Q8IWU2 (LMTK2) S1450 Uniprot
Q8NEB9 (PIK3C3) T159 Uniprot
Q8NEB9 (PIK3C3) T668 Uniprot
Q92558 (WASF1) S310 Uniprot
Q92558 (WASF1) S397 Uniprot
Q92558 (WASF1) S441 Uniprot
Q96KR7 (PHACTR3) S318 Uniprot
Q96RR4 (CAMKK2) S129 Uniprot
Q96RR4 (CAMKK2) S133 Uniprot
Q96RR4 (CAMKK2) S137 Uniprot
Q99490-2 (AGAP2) S249 Uniprot
Q99490 (AGAP2) S279 Uniprot
Q99719-2 (SEPT5) S17 Uniprot
Q9GZM8-1 (NDEL1) S198 Uniprot
Q9GZM8-1 (NDEL1) T219 Uniprot
Q9GZM8-1 (NDEL1) S231 Uniprot
Q9GZM8-1 (NDEL1) S242 Uniprot
Q9GZM8-1 (NDEL1) T245 Uniprot
Q9NQT8 (KIF13B) T506 Uniprot
Q9NQX3 (GPHN) S270 Uniprot
Q9NXR1 (NDE1) T191 Uniprot
Q9NZ72 (STMN3) S68 Uniprot
Q9NZ72 (STMN3) S73 Uniprot
Q9UD71-2 (PPP1R1B) T39 Uniprot
Q9UD71-1 (PPP1R1B) T75 Uniprot
Q9UM11 (FZR1) S40 Uniprot
Q9UM11 (FZR1) T121 Uniprot
Q9UM11 (FZR1) S163 Uniprot
Q9UQL6 (HDAC5) S279 Uniprot
Q9Y490 (TLN1) S425 Uniprot

研究背景

功能:

Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in post-mitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p53/TP53 in response to genotoxic and oxidative stresses enhances its stabilization by preventing ubiquitin ligase-mediated proteasomal degradation, and induces transactivation of p53/TP53 target genes, thus regulating apoptosis. Phosphorylation of p35/CDK5R1 enhances its stabilization by preventing calpain-mediated proteolysis producing p25/CDK5R1 and avoiding ubiquitin ligase-mediated proteasomal degradation. During aberrant cell-cycle activity and DNA damage, p25/CDK5 activity elicits cell-cycle activity and double-strand DNA breaks that precedes neuronal death by deregulating HDAC1. DNA damage triggered phosphorylation of huntingtin/HTT in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity. Phosphorylation of PXN reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Negative regulator of Wnt/beta-catenin signaling pathway. Activator of the GAIT (IFN-gamma-activated inhibitor of translation) pathway, which suppresses expression of a post-transcriptional regulon of proinflammatory genes in myeloid cells; phosphorylates the linker domain of glutamyl-prolyl tRNA synthetase (EPRS) in a IFN-gamma-dependent manner, the initial event in assembly of the GAIT complex. Phosphorylation of SH3GLB1 is required for autophagy induction in starved neurons. Phosphorylation of TONEBP/NFAT5 in response to osmotic stress mediates its rapid nuclear localization. MEF2 is inactivated by phosphorylation in nucleus in response to neurotoxin, thus leading to neuronal apoptosis. APEX1 AP-endodeoxyribonuclease is repressed by phosphorylation, resulting in accumulation of DNA damage and contributing to neuronal death. NOS3 phosphorylation down regulates NOS3-derived nitrite (NO) levels. SRC phosphorylation mediates its ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. May regulate endothelial cell migration and angiogenesis via the modulation of lamellipodia formation. Involved in dendritic spine morphogenesis by mediating the EFNA1-EPHA4 signaling. The complex p35/CDK5 participates in the regulation of the circadian clock by modulating the function of CLOCK protein: phosphorylates CLOCK at 'Thr-451' and 'Thr-461' and regulates the transcriptional activity of the CLOCK-ARNTL/BMAL1 heterodimer in association with altered stability and subcellular distribution.

翻译修饰:

Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by casein kinase 1 promotes kinase activity. By contrast, phosphorylation at Thr-14 inhibits activity.

Phosphorylation at Ser-159 is essential for maximal catalytic activity.

细胞定位:

Cytoplasm. Cell membrane>Peripheral membrane protein. Perikaryon. Cell projection>Lamellipodium. Cell projection>Growth cone. Cell junction>Synapse>Postsynaptic density.
Note: In axonal growth cone with extension to the peripheral lamellipodia (By similarity). Under neurotoxic stress and neuronal injury conditions, CDK5R (p35) is cleaved by calpain to generate CDK5R1 (p25) in response to increased intracellular calcium. The elevated level of p25, when in complex with CDK5, leads to its subcellular misallocation as well as its hyperactivation. Colocalizes with CTNND2 in the cell body of neuronal cells, and with CTNNB1 in the cell-cell contacts and plasma membrane of undifferentiated and differentiated neuroblastoma cells. Reversibly attached to the plasma membrane in an inactive form when complexed to dephosphorylated p35 or CDK5R2 (p39), p35 phosphorylation releases this attachment and activates CDK5.

Nucleus.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
组织特异性:

Isoform 1 is ubiquitously expressed. Accumulates in cortical neurons (at protein level). Isoform 2 has only been detected in testis, skeletal muscle, colon, bone marrow and ovary.

亚基结构:

Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity. Under neurotoxic stress and neuronal injury conditions, p35 is cleaved by calpain to generate p25 that hyperactivates CDK5, that becomes functionally disabled and often toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2 (By similarity). Interacts with AATK and GSTP1. Binds to HDAC1 when in complex with p25. Interaction with myristoylation p35 promotes CDK5 association with membranes. Both isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons. Interacts with EPHA4; may mediate the activation of NGEF by EPHA4. Interacts with PTK2/FAK1 (By similarity). The complex p35/CDK5 interacts with CLOCK. Interacts with HTR6 (By similarity).

蛋白家族:

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.

研究领域

· Human Diseases > Neurodegenerative diseases > Alzheimer's disease.

· Human Diseases > Substance dependence > Cocaine addiction.

· Organismal Systems > Development > Axon guidance.   (View pathway)

文献引用

1). Liu CC et al. CDK5 Regulates PD-L1 Expression and Cell Maturation in Dendritic Cells of CRSwNP. INFLAMMATION 2018 Sep 5 (PubMed: 30187339) [IF=5.1]

Application: IF/ICC    Species: human    Sample: nasal mucosal

Fig. 2. |The expression of CDK5 and PD-L1 in DCs of CRSwNPs. a Expression patterns of CDK5 and PD-L1 in nasal mucosal tissue of controlled,EosCRSwNP, and non-EosCRSwNP (×400 magnification; CDK5 stained in green; PD-L1 stained in red; nucleus stained in blue; scale bar = 100 μm).

2). Sui R et al. MiR-142-5p directly targets cyclin-dependent kinase 5-mediated upregulation of the inflammatory process in acquired middle ear cholesteatoma. Molecular Immunology 2022 Jan;141:236-245. (PubMed: 34875451) [IF=3.6]

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